Asthma, a growing health concern worldwide, particularly in industrialized countries, is a complex disease associated with an elevation of IgE production, abnormally high levels of Th2 cytokines, and airway inflammation. The immediate allergic asthmatic response is the release of histamine and leukotrienes from IgE-activated mast cells that leads to bronchoconstriction and airway hyperreactivity (AHR). Increased airway smooth muscle (ASM) contraction and reduced ASM relaxation in chronic asthma contributes to the excessive airway narrowing and AHR characteristic of asthmatic attacks.
Despite a better understanding of the pathophysiology of asthma, there are still considerable gaps in knowledge as well as a need for new classes of drugs. Current standard asthma management is primarily directed towards suppressing airway inflammation with inhaled corticosteroids (ICSs) and relieving bronchoconstriction with bronchodilators. This standard therapy controls symptoms in most, but not all asthmatic patients while on treatment. Severe asthma is difficult to control. ICSs are generally safe, however, their prolonged use, especially at high doses has been accompanied by concern about both systemic and local side effects. These include osteoporosis, hypothalamic-pituitary-adrenal axis suppression, immune suppression resulting in increased susceptibility to infections such as esophageal candidiasis and frequent upper respiratory tract infections in children, development of cataracts in elderly patients, mood changes, and pharyngitis. Long-term treatment with β2-adrenoceptor (β2-AR) agonists that directly relax ASM contraction, can result in bronchodilator resistance, cardiovascular diseases and arrhythmias. Therefore, development of new alternative or complementary therapies for this disease is becoming increasingly important.
In recent years, interest and use of complementary and alternative medicine (CAM) has been increasing. Traditional Chinese medicine (TCM) has a long history of human use in China and other Asian countries for treating and preventing diseases including asthma, and is part of accepted medical practice in these countries. TCM is also beginning to play a role in the US health care system. There is also increasing scientific understanding of the mechanisms of actions of certain TCMs for allergy and asthma. Kao et al. (2001) showed that the TCM formula xiao-qing-long-tang (XQLT) inhibited bronchoconstriction and airway eosinophil infiltration in ovalbumin-sensitized guinea pigs, and suppressed airway smooth muscle contraction (Kao et al., 2001).
ASHMI™ (Anti-asthma Herbal Medicine Intervention), an aqueous extract of Ganoderma lucidum (Fr.) P. Karst. (Ling Zhi), Sophora flavescens Aiton (Ku Shen) and Glycyrrhiza uralensis Fisch. ex DC (Gan Cao), has been shown to prevent allergic asthma airway hyperreactivity in mice and inhibit acetylcholine (ACh) induced airway smooth muscle (ASM) contraction in tracheal rings from allergic asthmatic mice.
We previously demonstrated that ASHMI™, an aqueous (aq.) extract of G. lucidum, S. flavescens and G. uralensis, eliminated both the immediate airway response and late-phase AHR, and significantly reduced pulmonary inflammation and airway remodeling in a murine allergic asthma model (Busse et al., 2010; Li et al., 2000; Zhang et al., 2010). In a clinical trial, ASHMI™ treatment reduced the use of β2-AR agonists, while significantly improving objective lung function and reducing symptom scores of asthmatics to a similar extent as conventional treatment, and showed a high safety profile (Kelly-Pieper K et al., 2009; Wen et al., 2005). We further found that, in addition to its anti-inflammatory effect, ASHMI™ inhibited ex vivo acetylcholine-induced ASM contractility in tracheal rings of allergic asthmatic mice without activating β2-ARs (Zhang et al., 2010). However, the individual constituent ingredients and compounds responsible for inhibiting ASM contraction have not been identified.
There is therefore a need in the medical arts for an identification and refinement of the bioactive constituents of the ASTHMI™ formula to reduce airway smooth muscle contractility.